| Vecuronium, an aminosteroid nondepolarizing neuromuscular blocking agent, has antagonistic properties that target the neuromuscular nicotinic acetylcholine receptor. Antagonists mimic endogenous agonists, in that they have affinity (propensity to bind) for a given receptor, but unlike agonists, they lack efficacy (ability to elicit response). Therefore, antagonists bind to receptors and prevent activation by an endogenous agonist. Acetylcholine is the endogenous agonist that targets both the neuronal nicotinic acetylcholine receptor and the neuromuscular nicotinic acetylcholine receptor. Hence, medications that antagonize neuromuscular nicotinic acetylcholine receptors may also antagonize neuronal nicotinic acetylcholine receptors.;Vecuronium has been linked to bradyarrythmias, hypotension, and cardiac arrest during anesthesia. (2,3) Vecuronium is a non-depolarizing neuromuscular blocking agent with competitive antagonistic affects at the neuromuscular nicotinic acetylcholine receptor, located post-synaptically in the neuromuscular junction. This research was designed to investigate vecuronium's affinity for the neuronal nicotinic acetylcholine receptors, located in the adrenal medulla and autonomic ganglia. Blockade of these receptors may be the cause of observed adverse cardiovascular responses seen clinically.;Inhibition of the neuronal nicotinic acetylcholine receptor in the adrenal medulla leads to a decrease in the amount of norepinephrine and epinephrine released into blood circulation. The physiologic effects of neuronal nicotinic acetylcholine blockade at the ganglia of the autonomic nervous system are determined by the predominant autonomic innervations (sympathetic vs. parasympathetic). If an organ is primarily innervated by the sympathetic nervous system, ganglia blockade will cause an exaggerated parasympathetic response. Ganglia blockade in an organ primarily innervated by the parasympathetic nervous system will cause an exaggerated sympathetic response.;Rat pheochromocytoma (PC-12) cells of the adrenal medulla were used as a model for human post-ganglionic neuronal and adrenal medulla cells because they contain neuronal nicotinic acetylcholine receptors. Varying concentrations of vecuronium were applied to cultured PC-12 cell media followed by carbachol, a neuronal nicotinic acetylcholine receptor agonist. Catecholamines (norepinephrine, dopamine) were extracted from the PC-12 cell media, washed, and purified in preparation for high performance liquid chromatography with amperometric detection.;In this study, vecuronium did not consistently inhibit catecholamine release from pheochromocytoma cells. Researchers found that vecuronium was devoid of statistically significant decreases in dopamine and norepinephrine release at most doses. However, a statistically significant decrease in dopamine release was observed at the intubating dose of vecuronium (0.1mg/kg).;From the data presented, vecuronium was devoid of a dose dependent effect on dopamine release at the vecuronium concentrations used. However, a significant reduction in dopamine release was observed at the intubating dose of vecuronium. At higher concentrations of vecuronium this reduction in dopamine was less apparent and not statistically significant. A possible mechanism behind vecuronium induced bradycardia/cardiac arrest was demonstrated. Further research is necessary. |
